A study of the role of Kv8.2 a novel potassium channel gene in retinal physiology and phototransduction

视觉的第一步是由位于视网膜后部的光感受器，即视杆细胞和视锥细胞捕获光子。人类视觉系统在从明亮的阳光到几乎完全黑暗的非常宽的光水平范围内工作。这需要相应的宽范围的灵敏度，并且视杆和视锥光感受器在生理上适于满足该需要。视锥细胞对光线相对不敏感，因此它们在白天提供视觉，不同的种类也提供色觉。另一方面，棒对光非常敏感，并且在非常低的光水平下操作。它们不提供任何颜色的感觉，因此物体在昏暗的光线下呈现单色。视锥细胞和视杆细胞的不同敏感性由细胞内的一系列过程决定。我们最近已经确定了编码钾通道蛋白Kv8.2的基因，该基因是一种致盲性疾病的基础，该疾病被描述为“视锥细胞营养不良伴超常视杆细胞视网膜电图（ERG）”。顾名思义，这种疾病会影响光感受器对光的敏感性，而光感受器对光的敏感性是在不同照明水平下看东西的能力的基础。钾（K+）通道蛋白是光感受器的电活动的中心，并且部分负责设置光感受器在黑暗中的电流。这直接关系到感光器对光的随后敏感性。该项目的目标是详细了解Kv8.2在光转导中的作用。将使用的方法将包括具有敲除突变的动物模型的研究和通道蛋白的体外研究。通过这种方式，我们将能够通过观察突变小鼠和正常小鼠光感受器的电活动来确定相关K+通道在完整视网膜中的作用。此外，对通道的体外活性的研究将确定其药理学和与其他蛋白质的相互作用。

The first step in vision is the capture of photons of light by the photoreceptors,t he rod and cones, that lie at the back of the retina. The human visual system operates over a very wide range of light levels from bright sunlight to almost complete darkness. This requires a corresponding wide range of sensitivity and the rod and cone photoreceptors are physiologiclly adapted to fulfill this need. Cones are relatively insensitive to light; they provide therefore vision in daylight the different classes also give colour vision. Rods on the other hand are very sensitive to light and operate at very low light levels. They do not provide for any perception of colour, hence objects appear monochromatic in dim light. The different sensitivities of cones and rods is determined by a range of processes that operate within the cells. We have recently identified the gene which encodes a potassium channel protein Kv8.2 that underlies a blinding disorder that is described as 'cone dystrophy with supernormal rod electroretinogram (ERG)'. As the named implies, the disorder affects the sensitivity of photoreceptors to light which is fundamental to the ability to see under different levels of illumination. Potassium (K+) channel proteins are central to the electrical activity of photoreceptors and are responsible in part for setting the current flow of the photoreceptors in the dark. This is directly related to the subseqent sensitivity of the photoreceptor to light. The objective of the project is to obtain a detailed understanding of the role of Kv8.2 in phototransduction. The approaches that will be used will include the study of an animal model with a knock-out mutation and in vitro studies of channel proteins. In this way, we will be able to define the role of relevant K+ channel in the intact retina from observations on the electrical activity of photoreceptors in mutant and normal mice. In addition, studies on the in vitro activity of the channel will define its pharmacology and interaction with other proteins.